Estrone - a partial estradiol antagonist in the normal breast

Area of Science:

• Endocrinology
• Oncology
• Pharmacology

Background:

• Oral hormone replacement therapy (HRT) with estradiol-17β (E2) increases circulating estrone (E1) levels.
• Estrone (E1) acts as an estrogen receptor agonist but may also antagonize estradiol (E2).

Purpose of the Study:

• To investigate the effect of circulating estrone (E1) on the association between estradiol (E2) and mammographic density (MD) increase.
• To explore the potential partial antagonist role of E1 in vivo.

Main Methods:

• 46 healthy post-menopausal women received daily oral E2 (2 mg) and norethisterone acetate (1 mg) for 6 months.
• Mammographic density (MD) and serum E1 and E2 levels were measured before and after treatment.
• Correlations between changes in E1, E2, and MD were analyzed.

Main Results:

• At high E1 levels, increases in MD positively correlated with increases in both E1 and E2.
• Reducing the upper E1 limit strengthened the correlation between E2 and MD increase.
• The significant correlation between E1 increase and MD increase disappeared when E1 levels were controlled.

Conclusions:

• Estrone (E1) may function as a partial E2 antagonist in normal breast tissue in vivo at high concentrations.
• E1 can interfere with the relationship between circulating E2 and biological estrogen effects.
• Structurally related compounds like E1 must be considered in studies of circulating steroids and their effects, especially at high concentrations.